Diet and Cancer Prevention

Home Foodtypes Mechanisms Treatments Specialists' Views Summary & Links Mechanisms After coming across the main groupings of nutrients implicated in the inhibition of carcinogenesis, here lay the cellular mechanisms involved in the process of this interface between nutrition and cancer, in order to get a more in-depth view of the matter. Oxidative damage Cells are susceptible to DNA damage when exposed to environmental factors, including mutagens, which can lead to tumourigenesis. See a simplified overview in Figure 1. Some of these substances that can damage DNA and cause cancer are known as free radical (FR) producers. These are charged or uncharged chemical species that have an unpaired electron in their outermost orbit and are therefore highly reactive, causing a chain of chemical reactions that damage cells. With the purpose of impeding this event, the adequate defence response is by the action of an antioxidant or by the binding of two FR. Other factors also engaged in mutagenesis and cancer development include reactive oxygen species (ROS - which result from oxidative phosphorylation reactions) and lipid radicals. Both these elements are by-products of cellular metabolism and respiration. FR are produced as a result of mitochondrial respiration but also by exogenous factors like drugs and environmental factors. They affect the metabolism of basic nutrients, which can cause changes in nucleic acids (DNA) and potentially lead to mutagenesis and subsequently tumour growth. An imbalance between FR generation and neutralisation occurs in certain pathological conditions and FR accumulate either due to excess production or lack of antioxidant bodies. This is when the administration of agents capable of counteracting FR or restoring innate defences is crucial to avoid organ dysfunction and tissue damage. Antioxidants fight against carcinogenesis A key solution is the presence of antioxidants, which are natural compounds found in aqueous and lipid parts of the body. They inactivate and 'scavenge' such radicals, and can be classified into: Intrinsic antioxidant enzymatic systems (such as Gluthianone transferases and Catalases), being the first line of protection against oxidative damage and capable of antagonising the initiation of carcinogenesis. They are known to decrease in concentration with age, fact that could hypothetically be associated with the late onset of degenerative and carcinogenic diseases. Nonenzymatic antioxidants, encompassing a wide selection of substances found in the human diet (including vitamins A, C and E, carotenoids, glutathione and selenium). FR can cause mutations, deletions, gene amplifications, and rearrangements in the sequence of DNA, triggering the activation of various proto-oncogenes and/or tumour suppressor genes. Chemical and conformational changes in DNA, and specially oxidative damage to specific points of polymerase (responsible for the duplication of DNA), are common lesions which give rise to mutations. It is thought that there is a temporal relationship between oxidative stress, genomic instability and the development of cancer. See Figure 2. Most of the alterations that are produced in the mitochondrial genome can boost the generation of ROS because of altered production of essential components (antioxidant enzymes). This impairment contributes not only to the process of ageing, but also to tumourigenesis. Nonetheless, FR are also used beneficially in immune responses to destroy invading bacteria and other pathogens. Antioxidants play a major role in the inactivation of FR, by 'scavenging' them. Some prevent initiation of the oxidation process, while others inhibit the cascade of oxidation reactions. Free radicals are reduced by means of oxidation of vitamins, which prevents lipid peroxidation in the cell membrane. For a clearer idea on how these compounds act upon the radicals, please see Figure 3.